Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors

Candace D. Middlebrooks, A. Rouf Banday, Konichi Matsuda, Krizia Ivana Udquim, Olusegun O. Onabajo, Ashley Paquin, Jonine D. Figueroa, Bin Zhu, Stella Koutros, Michiaki Kubo, Taro Shuin, Neal D. Freedman, Manolis Kogevinas, Nuria Malats, Stephen J. Chanock, Montserrat Garcia-Closas, Debra T. Silverman, Nathaniel Rothman, Ludmila Prokunina-Olsson

研究成果: Article査読

97 被引用数 (Scopus)

抄録

High rates of APOBEC-signature mutations are found in many tumors, but factors affecting this mutation pattern are not well understood. Here we explored the contribution of two common germline variants in the APOBEC3 region. SNP rs1014971 was associated with bladder cancer risk, increased APOBEC3B expression, and enrichment with APOBEC-signature mutations in bladder tumors. In contrast, a 30-kb deletion that eliminates APOBEC3B and creates an APOBEC3A-APOBEC3B chimera was not important in bladder cancer, whereas it was associated with breast cancer risk and enrichment with APOBEC-signature mutations in breast tumors. In vitro, APOBEC3B expression was predominantly induced by treatment with a DNA-damaging drug in bladder cancer cell lines, and APOBEC3A expression was induced as part of the antiviral interferon-stimulated response in breast cancer cell lines. These findings suggest a tissue-specific role of environmental oncogenic triggers, particularly in individuals with germline APOBEC3 risk variants.

本文言語English
ページ(範囲)1330-1338
ページ数9
ジャーナルNature Genetics
48
11
DOI
出版ステータスPublished - 01-11-2016
外部発表はい

All Science Journal Classification (ASJC) codes

  • 遺伝学

フィンガープリント

「Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル